Method and apparatus for electrically stimulating the nervous system to improve ventricular dysfunction, heart failure, and other cardiac conditions

ABSTRACT

A method and apparatus are used to provide therapy to a patient experiencing ventricular dysfunction or heart failure. At least one electrode is located in a region associated with nervous tissue, such as nerve bundles T 1 -T 4 , in a patient&#39;s body. Electrical stimulation is applied to the at least one electrode to improve the cardiac efficiency of the patient&#39;s heart. One or more predetermined physiologic parameters of the patient are monitored, and the electrical stimulation is adjusted based on the one or more predetermined physiologic parameters.

RELATED CASES

This case claims priority to the following provisionally-filed cases:

U.S. Provisional Patent Application Serial No. 60/294,072, filed May 29,2001, entitled “Closed-Loop Neuromodulation for Prevention and Treatmentof Cardiac Conditions”;

U.S. Provisional Patent Application Serial No. 60/243,393, filed Oct.26, 2000, entitled “Method and Apparatus to Minimize the Effects of aCardiac Insult”;

U.S. Provisional Patent Application Serial No. 60/243,536, filed Oct.26, 2000, entitled “Method and Apparatus to Minimize the Effects of aCardiac Insult”; and

U.S. Provisional Patent Application Serial No. 60/243,609, filed Oct.26, 2000, entitled “Method and Apparatus for Electrically Simulating theNervous System to Improve Ventricular Dysfunction, Heart Failure, andOther Cardiac Conditions”, all of which are incorporated herein byreference in their entireties.

This case is related to, and contains subject matter in common with thefollowing applications:

U.S. patent application Ser. No. 09/999,722 filed on Oct. 26, 2001entitled “Method and Apparatus to Minimize the Effects of a CardiacInsult”, and published as US 2003/0004549.

U.S. patent application Ser. No. 09/999,723 filed on Oct. 26, 2001entitled “Method and Apparatus to Minimize the Effects of a CardiacInsult”, now U.S. Pat. No. 7,010,345.

U.S. patent application Ser. No. 10/035,319 filed on Oct. 26, 2001entitled “Closed-Loop Neuromodulation for Prevention and Treatment ofCardiac Conditions”, and published as US 2002/0165586, now issued asU.S. Pat. No. 7,218,964.

FIELD OF THE INVENTION

This invention relates to a method and apparatus for electricallystimulating certain nervous tissue to alter conditions within the heart,and, more particularly, to stimulate nerves to treat ventriculardysfunction or heart failure.

DESCRIPTION OF THE RELATED ART

Various cardiac conditions, such as supraventricular arrhythmias, anginapectoris, and ventricular dysfunction or heart failure, have beentreated by electrical stimulation of the spinal cord, vagus and othernerves. Typically, electrodes are implanted in the patient adjacent thespinal area and electrically excited to produce desirable effects on thefunctioning of the heart. For example, a paper entitled “Vagal Tuning”by Bilgutay et. al., published in the Journal of Thoracic andCardiovascular Surgery, Vol. 56, No. 1, July 1968, pp. 71-82, discussesa system that delivers electrical stimulation to the vagus nerve usingsilastic coated, bipolar electrodes, such as those described in U.S.Pat. No. 3,421,511. The electrodes are surgically implanted around theintact nerve or nerves and a controlled current is delivered thereto.The electrodes pass the current to the nerve(s), producing a decreasedheart rate while still preserving sinus rhythm in the patient. Lowamplitude stimulation has also been employed to control inducedtachycardias and ectopic beats.

Angina pectoris and paroxysmal atrio-ventricular junctional orsupraventricular tachycardias have also been treated by stimulating thecarotid sinus nerve via implanted electrodes. For example, a paperentitled “Carotid Sinus Nerve Stimulation in the Treatment of AnginaPectoris and Supraventricular Tachycardia,” published in CaliforniaMedicine, 112:41-50, March 1970, describes a system in which patientsmay electrically stimulate their carotid sinus nerve when they senseangina and/or supraventricular tachycardia.

Delivery of electrical stimulation to the nervous system using animplanted electrode has been found particularly effective in the reliefof chest pain, such as angina pectoris, that often accompaniesmyocardial ischemia. For example, U.S. Pat. No. 5,058,584 to Bourgeois,incorporated herein by reference in its entirety, discloses a system andmethod for treating such chest pain using electrical stimulation withinthe epidural space of the spinal cord. This treatment is provided onlyafter a symptomatic level of activity is reached as sensed by anaccelerometer or other activity sensor. Similarly, U.S. Pat. No.6,058,331 to King, also incorporated herein by reference in itsentirety, discusses a system and method for treating ischemia byautomatically adjusting electrical stimulation to the spinal cord,peripheral nerve, or neural tissue ganglia based on a sensed patientcondition. U.S. Pat. No. 5,199,428 to Obel et al., incorporated hereinby reference in its entirety, discloses a system for stimulating theepidural space with continuous and/or phasic electrical pulses using animplanted pulse generator upon the detection of myocardial ischemia todecrease cardiac workload, and thereby reduce cell death related to theischemic event. U.S. Pat. No. 5,824,021 to Rise, incorporated herein byreference in its entirety, discusses a system and method for providingspinal cord stimulation to relieve angina, and to further provide apatient notification that an ischemic event is occurring. This spinalcord stimulation is provided only after the ischemia is alreadydetected.

In addition to the above-described systems, other systems have beendisclosed to provide nerve stimulation following the onset ofpredetermined condition. U.S. Pat. No. 6,134,470 to Hartlaub describes asystem for utilizing spinal cord stimulation to terminatetachyarrhythmias. The stimulation is provided only after thetachyarrhythmias, or a precursor thereto, has been detected. U.S. Pat.No. 3,650,277 discloses a system for stimulating the left and rightcarotid sinus nerves in response to the detection of elevated meanarterial blood pressure to alleviate hypertension.

Although it is known that ischema and certain arrhythmias may be treatedusing electrical stimulation of the nervous system via implantedelectrodes, it has not heretofore been known to utilize electricalstimulation of nerves or other body tissue to treat ventriculardysfunction, heart failure, or imbalance of autonomic tone orneuro-endrocrinological system in a manner that improves cardiacperformance and efficiency of the heart.

Typically, patients with ventricular dysfunction or heart failure have areduced capacity for myocardial function. The heart is unable toadequately meet the metabolic demands of the body by providing theappropriate blood flow. This may result in increased blood pressure(afterload), and increased volume retention (preload). Thus, commonsymptoms of ventricular dysfunction or heart failure include fatigue,which is caused by the low cardiac output, and edema and swelling, whichis caused by fluid overload.

Ventricular dysfunction or heart failure is predominantly the result ofan imbalance in the neuro-endrocrinological systems, including thesympathetic and the renin-angiotensin systems. Prior methods oftreatment include the administration of drugs that interfere with thecyclical nature of the neuro-endocrine feedback. For example, ACEinhibitors may be prescribed to decrease the effects of angiotensin Iand II, and to reduce the afterload and preload. Beta-blockers have alsobeen shown to reduce afterload, and may further decrease contractility.This provides greater relaxation for the heart myocardium.

Treating ventricular dysfunction or heart failure through theprescription of drugs, however, is problematic. The dosages are patientdependant, and thus titration of the drug amounts must be performed on apatient-by-patient basis. Generally, this involves invasive ornon-invasive follow-up procedures, and a reassessment of the treatment.This type of trial-and-error process may be lengthy and frustrating.Additionally, many patients experience unpleasant side-effects from someventricular dysfunction or heart failure medications. For example, someasthmatics cannot take beta-blockers because of global side effects dueto contra-indications. Moreover, effective treatment in this situationdepends on patient compliance with the prescribed treatment dosages andschedules. However, not all patients comply with the recommendations oftheir physician. What is needed, therefore, is an alternative treatmentthat may be used to replace, or to augment, the administration of drugsin treating ventricular dysfunction or heart failure or imbalance ofautonomic tone.

SUMMARY OF THE INVENTION

In one aspect of the instant invention, a method is provided fortreating ventricular dysfunction, heart failure, or imbalance ofautonomic tone or neuro-endrocrinological system. At least one electrodeis provided in a region associated with nervous tissue in a patient'sbody. Electrical stimulation is provided via the at least one electrodeto improve the cardiac performance (e.g. hemodynamics) and efficiency(e.g. balance between supply and demand) of the patient's heart.

In another aspect of the instant invention, an apparatus is provided fortreating ventricular dysfunction, heart failure, or imbalance ofautonomic tone. At least one electrode is located in a region associatedwith nervous tissue in a patient's body. Means are included for applyingelectrical stimulation via the at least one electrode to improve thecardiac performance and efficiency of the patient's heart.

In still another aspect of the instant invention, a method is provided.The method comprises providing at least one electrode in a regionassociated with nervous tissue in a patient's body. Electricalstimulation is applied via the at least one electrode to alter thefunctioning of a patient's heart. One or more predetermined physiologicparameters of the patient are monitored, and the electrical stimulationis adjusted based on the one or more predetermined physiologicparameters.

In another embodiment, an apparatus is provided comprising at least oneelectrode that may be positioned in a region associated with nervoustissue in a patient's body. Means for controlling the delivery ofstimulation to alter functioning of a patient's heart is also provided.The controlling means is capable of utilizing one or more predeterminedphysiologic parameters of the patient, and the electrical stimulation isadjusted based on the one or more predetermined physiologic parameters.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be understood by reference to the followingdescription taken in conjunction with the accompanying drawings, inwhich the leftmost significant digit(s) in the reference numeralsdenote(s) the first figure in which the respective reference numeralsappear, and in which:

FIG. 1A illustrates a stylized representation of a posterior view of apatient with electrodes positioned thereon.

FIG. 1B illustrates a stylized representation of an anterior view of apatient with electrodes positioned thereon.

FIG. 1C is a diagram illustrating an implantable stimulation deviceimplanted within a patient.

FIG. 2 illustrates a stylized block diagram of a controller of FIG. 1.

FIG. 3 illustrates a stylized flowchart of a control routine that may beperformed by the controller of FIGS. 1 and 2.

FIG. 4 is a flowchart illustrating one embodiment of the currentinvention.

FIG. 5 is a flowchart illustrating one embodiment of concomitant therapydelivery that may be provided in conjunction with neural stimulation.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

Illustrative embodiments of the invention are described below. In theinterest of clarity, not all features of an actual implementation aredescribed in this specification. It will of course be appreciated thatin the development of any such actual embodiment, numerousimplementation-specific decisions must be made to achieve thedevelopers' specific goals, such as compliance with system-related andbusiness-related constraints, which will vary from one implementation toanother. Moreover, it will be appreciated that such a development effortmight be complex and time-consuming, but would nevertheless be a routineundertaking for those of ordinary skill in the art having the benefit ofthis disclosure.

Illustrative embodiments of a method and apparatus for providingimproved cardiac function according to the present invention are shownin the Figures. As will be readily apparent to those skilled in the artupon a complete reading of the present application, the present methodand apparatus are applicable to a variety of systems other than theembodiment illustrated herein.

Generally, the instant invention is directed to a method and apparatusfor improving cardiac performance (e.g., hemodynamics) and efficiency(e.g., balance between supply and demand and balance within theneuro-endrocrinological systems) of the patient's heart. In theillustrated embodiment, the current invention utilizes electricalstimulation to treat ventricular dysfunction or heart failure. As shownin FIGS. 1A and 1B, a system 100 may provide stimulation (e.g. SCS,TENs, sub-cutaneous) to a patient 102 adjacent one or more of thelocations T1-T12, and C1-C8 or to nerves on the chest, to improvecardiac performance and efficiency. Such stimulation has been shown toimprove cardiac contractility, to further improve the pressure-volumerelationship within the heart, to reduce sympathetic activity of thecardiac tissue, to improve the cardiac condition, and to reduce thelikelihood of ventricular arrhythmias. Thus, the electrical stimulationproduces effects similar to those induced by prescriptionbeta-adrenergic receptor blocking drugs. SCS has been shown tovasodilate peripheral arterioles and increase blood flow to the limbs.SCS may further cause the production of neuropeptides such as CGRP, NO,and VIP that are known vasodilators, which may assist in redirection ofblood flow from regions of high flow to regions of low flow. Thisfurther improves the performance and efficiency of the heart. In theischemic dilated cardiomyopathy patients, this therapy may suppress orreduce sub-endocardial ischemia, and hence be cardio-protective.Electrical stimulation may further result in improvements in operationalefficiency and function of cardiac tissue even in the presence ofreduced blood supply.

A controller 104 is coupled through conventional conductive links 106,such as leads or wires, to one or more electrodes 108 mounted in aregion adjacent the T1-T12 and C1-C8 vertebrae and their associatednerve bundles. The electrodes 108 may take on any of a variety of forms,including but not limited to conventional surface mounted electrodes,such as are commonly used in conjunction with Transcuteous NeurologicalStimulators (TENS) units. These surface mounted electrodes may be fixedto the patient 102 via any of a variety of conventional mechanical orchemical mechanisms or may be simply held in place by friction andgravity. Alternatively, conventional implantable electrodes may besurgically inserted into the spinal region adjacent the T1-T12 and C1-C8vertebrae, and may be located near or even immediately adjacent theT1-T12 and C1-C8 nerve bundles for spinal cord stimulation.

Implantable electrodes may be placed subcutaneously to stimulateunderlying muscles, overlying cutaneous nerves, or passing somaticnerves. For example, lead Model 3987, On Point®, is a peripheral nervestimulation lead available from Medtronic, Inc. with four contacts and apolyester mesh skirt for fixation to subcutaneous tissue or musclefascia. Other Medtronic leads might also be used, including Model 3587Aor Model 3998, which have an insulative paddle enlargement, or Model3487A or Model 3888, which do not. In both surface mounted and implantedelectrodes, electrical signals supplied by the controller 104 to theelectrodes 108 electrically stimulate nervous tissue in the spinalcanal.

Implantable electrodes may be placed adjacent to nerves such as themedian, peroneal, ulnar, and ansalenticularis nerves to providestimulation according to the current invention. Similarly, implantableelectrodes may be placed near the vagus nerves, carotid sinus, and allother cranial nerves to provide stimulation. Finally, implantableelectrodes may be placed epicardially or transvenously near the cardiacganglia or plexi and also employed in this manner.

The controller 104 may take the form of an external device or animplantable device. Where the controller 104 is an external device, itmay be useful in providing therapeutic signals to a patient who isexperiencing an unexpected cardiac event, such as a first or otherwiseunanticipated episode of ventricular dysfunction, heart failure,cardiovascular collapse, etc. However, where the patient has a historyof cardiac events, it may prove useful to construct the controller 104in a housing designed to be implantable within the human body, such asis common in cardiac pacemakers and defibrillators. The controller 104may be programmed for either automatic or manual operation. That is, thecontroller 104 may have one or more conventional sensors (not shown) ofa type capable of sensing a cardiac event or a precursor to a cardiacevent in the patient, e.g., a decompensation episode of ventriculardysfunction, heart failure, and cardiovascular collapse. The sensors andcontrol scheme used to detect the cardiac event or a precursor to acardiac event may be conventional, such as is found in implantabledefibrillators or pacemakers. Upon detection of the cardiac event, thecontroller 104 may automatically begin therapeutic treatment of thepatient by electrically stimulating the T1-T12 nerve bundles.Alternatively, a patient or authorized person may manually activate thecontroller 104 to begin this therapeutic treatment. Manual activationmay be accomplished by any of a variety of mechanisms. For example,where the controller 104 is implanted in the patient, activation may beaccomplished by wireless communication or the like.

In those situations in which a patient has a history of cardiac events,it is generally useful to construct the controller 104 in a housing 105designed to be implantable within the human body, as shown in FIG. 1C.In this embodiment, implanted lead 106 c is employed to deliver SCSaccording to the invention. This housing may optionally include a pacingand/or cardioverter/defibrillator stimulation circuit for generatingcardiac stimulation signals to the heart 107 using one or more leads109, as is known in the art. Leads 109 may carry one or morephysiological sensors 111 for sensing physiological signals, as isdiscussed below. Additionally, or in the alternative, the housing mayalso include a drug delivery device such as a drug pump coupled to adrug delivery catheter that may be used with the nerve stimulation toprovide a biologically-active agent to tissue to prevent anticipated ordetected physiological insults.

The therapeutic treatment administered by the controller 104 may take ona variety of different forms. In one embodiment, SCS may be used totitrate the pressure-volume relationship of the heart in conjunctionwith other types of therapy, such as one or more types of pacingtherapies. For example, an adjustment of the Atrial-to-Ventricular andVentricular-Ventricular timing during atrial-synchronized bi-ventricularpacing (cardiac resynchronization therapy) may be performed at about thesame time as the SCS to further improve the performance and efficiencyof the heart.

Additionally, the stimulation therapy may be administered along withcardiac resynchronization therapy to further improve the cardiacperformance and efficiency of the heart. That is, the SCS or anotherstimulation (e.g. TENs, subcutaneous) therapy may be administer shortlybefore, shortly after, or at the same time as resynchronization or otherpacing therapy. For example, the SCS therapy may be administered inconjunction with bradycardia pacing therapy, such as changes in thelower rate limit (LRL—atrial or ventricle); therapies for increasingcardiac output or pulse pressure, such as post extra-systolicpotentiation (PESP) pacing or non-excitatory stimulation (NES) pacing;and/or therapies for preventing arrhythmias or reducing arrhythmicburden, such including arrhythmia prevention pacing algorithms, such asconsistent A or V pacing and rate stabilization pacing. In particular,one exemplary scheme involves administering the stimulation therapy inconjunction with overdrive RV apical pacing to provide improved cardiacoutput for example in patients with obstructive cardiomyophathies. Inaddition, the therapy may be administered in conjunction with otherdevice therapies to further improve the cardiac performance andefficiency of the heart. These device therapies may include, but are notlimited to, drug delivery device therapies, automatic externaldefibrillation therapies, treatments provided by monitoring ordiagnostic devices, and therapies provided in conjunction with patientmanagement and information tools.

In one embodiment, delivery of the SCS therapy may be modified based ona variety of measurable physiologic parameters. As depicted in FIGS. 1Aand 1C, representative sensors 110 and/or 111 may be positioned adjacentor within the body of the patient 102 to sense various physiologicalconditions, which are communicated back to the controller 104 over leads112. The measured physiological conditions may be used as an indicationof the patient's response to the therapy being administered by thecontroller 104. That is, a positive physiological response may be usedas an indication that the therapy is achieving the desired result. Thesensed physiological conditions may be used to adjust the parameters ofthe SCS. For example, the controller 104 may measure and record cardiacpressure. A change in the cardiac pulse pressure may be used in aclosed-loop system to adjust delivery of SCS. For example, if thecontroller 104 detects that the cardiac pulse pressure has declined overtime, then the parameters of the SCS may be adjusted in an attempt toincrease the cardiac pulse pressure. On the other hand, where thecontroller 104 observes a consistent, appropriate cardiac pulsepressure, then the stimulation delivered to the T1-T12 nerve bundles maybe continued, as a desired result is being achieved by the SCS. On theother hand, where the controller 104 observes continued high, or evenrising, cardiac pulse pressure, then the parameters of the SCS may beadjusted in an attempt to lower the cardiac pulse pressure over time.

Other parameters that may be measured and used as feedback in a closedloop control system for the SCS include, but are not limited to,pressure-volume (PV) loops, pressure-area (PA) loops, pressure-dimension(PD) loops, diastolic and systolic pressures, estimated pulmonary arterypressure, change in cardiac pulse pressure, pre-ejection timingintervals, heart rate measures (such as, rates, intervals, and thelike), autonomic indicators (such as, heart rate variability, directneural recordings, and the like), chemical sensors (such as,catecholamines, O2, pH, CO2, and the like), or non-cardiac physiologicsensors (such as, activity, respiratory rate, time of day, and thelike). Those skilled in the art will appreciate that any of a widevariety of measurable physiologic parameters may be monitored and usedto implement the closed-loop adaptive controller described herein. Anexemplary controller is described in greater detail in co-pending U.S.application No. 10/035,319, entitled “Closed-Loop Neuromodulation forPrevention and Treatment of Cardiac Conditions” filed on even dateherewith, and which is hereby incorporated by reference in its entirety.

Any combination of the foregoing may be used to determine the timing,waveforms, and amplitude of the electrical stimulation delivered to theelectrodes 108. Those skilled in the art will appreciate that theillustrated, representative sensor 110 may take on any of a variety offorms, depending upon the physiological parameter being sensed.Generally, these feedback parameters may be detected and used to controlcertain parameters of the stimulation, such as the magnitude, duration,duty cycle, and frequency. Typically, the stimulation falls within therange of about 200-400 microsecond duration pulses, at a frequency inthe range of about 50-100 Hz, and at a voltage of up to about 6V. Forexample, with greater stimulation parameters (increased magnitude,increased frequency, increased duty cycle, and/or increased pulsedurations, there is a potential for greater beta-blocker type(withdrawal of sympathetic activity) effect. This would result indecreased contractility, alteration in blood flow (increase in coronarysupply), improved cardioprotection and decreased workload or demand. Anadditional example is the appropriate use of pre-set parameters inresponse to sensed cardiac event information of the patient. Forexample, if the patient is having a decompensation ventriculardysfunction or heart failure event, then “more strenuous” stimulationparameters (e.g. increased magnitude, increased pulse width andincreased frequency) may be used to provide the greatest amount ofprotection and local withdrawal of sympathetic activity. For a lesssevere event, such as an elevation in end diastolic pressure, then “lessstrenuous” stimulation parameters may be used to provide an incrementaladjustment to the cardiac function.

FIG. 2 illustrates a block diagram of one embodiment of the controller104. Generally, the controller 104 is comprised of one or more drivercircuits 200 and receiver circuits 202. The driver circuits 200 aregenerally responsible for providing the stimulating signals over thelines 106 to the electrodes 108. That is, a processor 204, operatingunder software or hardware control, may instruct the driver circuit 200to produce a stimulating signal having a set of preselected, desiredparameters, such as frequency, duty cycle, duration, waveform shape,amplitude, voltage and magnitude. As noted above, driver circuits 200may optionally include circuits 201 to generate pacing and/orhigh-voltage stimulation (denoted schematically in FIG. 2 as a part ofdriver circuit 200) to the heart on leads 109.

The receiver circuits 202 are generally responsible for receivingsignals over the lines 112 from the sensors 110 and 111, and processingthose signals into a form, such as a digital format, which may beanalyzed by the processor 204 and/or stored in a memory 206, such as adynamic random access memory (DRAM). The memory 206 may also storesoftware, which is used to control the operation of the processor 204.

In one embodiment, signals stored in memory 206 may be transferred via acommunication circuit 207 such as a telemetry circuit to an externaldevice 209 such as a programmer. These signals may be stored in theexternal device, or transferred via a network 211 to a remote system 213which may be a repository or some other remote database. Network 211 maybe an intranet, internet system such as the world-wide web, or any othertype of communication link.

As noted above, controller 104 may further include a drug deliverydevice 217 that may comprise a pump coupled to a catheter 215. Exemplaryimplantable drug delivery systems that may be adapted to deliverbiologically-active agents in conjunction with SCS or other nervestimulation are disclosed in U.S. Pat. No. 5,607,418, issued toArzbaecher, U.S. Pat. No. 5,220,917, issued to Carnilli, U.S. Pat. No.4,146,029, issued to Ellinwood and U.S. Pat. No. 5,330,505, issued toCohen, all incorporated herein by reference in their entireties.

The overall general operation of the controller 104 may be appreciatedby reference to a flowchart depicted in FIG. 3. Those skilled in the artwill appreciate that the flowchart illustrated herein may be used torepresent either software that may be executed by the processor 204 orhardware configured to operate to perform the functions set forth in theflowchart. The process depicted in FIG. 3 begins at block 300 with theassumption that a cardiac event may have been detected eitherautomatically or manually, but in any event, therapy is beingadministered by the controller 104.

At block 300, the processor 204 receives the measured physiologicalparameters via the receiver circuits 202. At block 302, the processor204 compares the measured parameters to corresponding desired ranges. Ifthe measure parameters are within the desired range, as determined atblock 304, the processor 204 returns to block 300 and the processrepeats. On the other hand, if the measured parameters fall outside thedesired range, then the processor 204 at block 306 adjusts thestimulation parameter, which should result in the physiologicalparameters of the patient being adjusted to fall within the desiredrange. Thereafter, the process returns to block 300 and the processbegins anew.

It should be appreciated that, owing to physiological differencesbetween patients, an adjustment to the stimulation parameters may notproduce an immediate, precise change in all patients. Rather, it isanticipated that each patient will respond substantially uniquely tovariations in the stimulation parameters. Thus, it may be useful to addcontrollable variability to the operation of the feedback arrangementdescribed herein. For example, it may be useful to control the rate atwhich the stimulation parameters are allowed to change, or to develop ahistogram for a particular patient. The inventive system could includethe ability to record parameters associated with the delivered SCS suchas pulse widths, frequencies, duty cycles, and time varying patterns.These parameters and the patient's response may be recorded in thememory 206, for example. Based on patient response, the efficacy of theSCS can be evaluated so that the delivered SCS can be adjusted tofurther improve cardiac performance and efficiency. This “learning”capability allows the system to optimize SCS delivery based on priorpatient data so that treatment is automatically tailored to individualpatient needs. Furthermore, within a particular patient it may be usefulfor the device to tailor its therapy based on prior learning. Forexample, the onset or character of cardiac events may differ fromepisode to episode. It may be useful for the system to recognizemultiple types of events (differing in, for example, severity, rate ofonset, time of day or occurrence, patient activity levels, etc.) andtreat these events with a uniquely tailored set of treatment parameters.Again, the device memory may be used to record parameters and patientresponses to tailor treatments to different patterns of parameters.

In an alternative embodiment, a combined neuro and pacing stimulatorImplantable Pulse Generator with outputs for neural stimulation (e.g.SCS, TENs, sub-cutaneous, peripheral, etc.) is provided. Leadattachments may be provided, in one instance, by a PISCES QUAD-type leadcommercially-available from Medtronic Corporation, or an equivalent.Stimulation may be used in conjunction with cardiac resynchronization orother pacing therapy to improve cardiac function and may further beoptimized based on some diagnostic parameter such as pressure,impedance, volume, or dimension, as discussed above. The ImplantablePulse Generator may further include a drug delivery system so that drugtherapy to improve cardiac function may be automatically titrated withthe stimulation. The implantable pulse generator may further includes apatient monitoring, diagnostic, or management system so that diagnosticand patient information therapy to improve cardiac function may be usedin conjunction with neural stimulation.

In another embodiment, Spinal Cord Stimulation (SCS) may be performed atcervical levels C1-C8 instead of, or in addition to, T1-T12 stimulation.In yet another embodiment, Peripheral Nerve Stimulation (PNS) may beperformed at C2, C3, median, peroneal, ulnar, ansa lenticularis, and/ordorsal root ganglia to improve cardiac performance and efficiency.

In all of the above-described embodiments, the electrical stimulation isdescribed as SCS, which may be delivered using one or more implantedelectrodes located adjacent the spine, for example. However, it will beunderstood that stimulation using externally-applied electrodes, orsubcutaneous electrodes located under the skin may also be used toobtain the benefits discussed above. In the case of anexternally-applied electrode system, a portable stimulation devicecarried or worn externally by the patient may be used to providetreatment.

In one embodiment, a paddle-type (flat) lead having a surface areabetween one square cm and five square inches or more may be used toaccomplish the subcutaneous stimulation. Such a lead may be formed of aninsulative material, with programmable electrodes on one or more of theflat sides of the lead for either skin stimulation, muscle stimulation,or both.

In one embodiment, electrodes may be provided on both sides of the lead,with the electrodes employed for stimulation at a given time beingselectively enabled by a user. Alternatively, the system may beprogrammable to select the type of tissue to be stimulated. This isdesirable since in some instances, it may be beneficial to providestimulation to only spinal neurons, whereas in other instances it may bedesirable to also stimulate skin nerves, muscle nerves, peripheralnerves, cranial nerves, such as the vagus, ganglia and plexi, or anycombination of such nervous tissue. Various electrode combinations couldbe provided to allow for selectively enabling the stimulation in thismanner.

In another embodiment, the paddle-type lead is between four and tenmillimeters wide to easily pass through a twelve-gage needle before itunfolds. A special needle may be provided having an oval or rectangularcross-section of appropriate size to allow for the delivery of this typeof lead. Electrodes may be provided on one or both sides of the paddlelead. In yet another embodiment, the electrodes of a cutaneousstimulation system could be placed on the chest wall, or a stimulationsource may be attached to leads passed via needles to one or moresubcutaneous sites. Alternatively, electrodes may be placed on anoutside surface of an implanted pulse generator or pacing device or maybe of the type integrally formed with the can, shell, or housing of animplantable device.

FIG. 4 is a flowchart illustrating one embodiment of the currentinvention. A cardiac event such as ventricular dysfunction, heartfailure, or imbalance of autonomic tone or neuro-endrocrinologicalsystem may be detected using measurable parameters such as increaseddiastolic pressure, a lower heart rate variability, increasedcatecholiamine levels, or a change in naturetic peptide levels (400). Ifa cardiac event is detected, any concomitant therapies are performed(402). If neural stimulation is not on (404), it is activated (406).This therapy delivery may involve use of artificial intelligence orother learning capability, as discussed above. Monitoring continues todetermine whether the cardiac condition still exists (400). Returning tostep 404, if neural stimulation is already on, stimulation parametersmay be adjusted using physiological signals that may be sensed bysensors 110 and 111 (408), and monitoring continues with step 400.

In block 400, if a cardiac event has terminated, processing continues tostep 410, where it is determined whether stimulation is on. If not,processing continues with monitoring step 400. Otherwise, stimulationdeactivation is initiated (412). This may involve a hysteresis so thatstimulation is terminated gradually over a predetermined period of time.

FIG. 5 is a flowchart illustrating one embodiment of concomitant therapydelivery that may be provided in conjunction with neural stimulation.This therapy corresponds to that shown in step 402 of FIG. 4. This typeof therapy may involve pacing, defibrillation, drug delivery,monitoring, and/or patient management therapies, for example (500). Ifsuch a therapy is not enabled, no action is taken (502). Otherwise, ifthe therapy is on therapy parameters may be adjusted (506). This may beperformed using sensed physiological parameters, for example. If therapyis not enabled, this therapy is activated (508). Therapy delivery may bebased on the results of previously-delivered therapy in the mannerdiscussed above, as may be accomplished using artificial intelligencecapabilities, for example. In either event, processing continues bycomparing the cumulative effects of neural stimulation and the othertherapy delivery so that the therapy delivery may be adjusted, ifnecessary (510). For example, delivery of stimulation to nerve tissuecould increase pacing thresholds associated with a concomitant pacingtherapy. As a result, the pacing therapy may need to be adjusted. Inanother example, delivery of stimulation according to the currentinvention may reduce pulse pressure, whereas a bi-ventricular pacingregimen increases the pulse pressure. It may be desirable to monitorthis interaction and adjust one or more therapies as needed. This stepis performed using information provided by the sensors, the neuralstimulation system, and the concomitant therapy system(s), as shown inblock 512.

From the foregoing discussion, one skilled in the art will appreciatethat the current system and method for treating ventricular dysfunction,heart failure, or imbalance of the autonomic tone allows the treatmentto be titrated without regard to a patient's compliance. Additionally,more patients will be able to use the therapy because of general lack ofside-effects.

The particular embodiments disclosed above are illustrative only, as theinvention may be modified and practiced in different but equivalentmanners apparent to those skilled in the art having the benefit of theteachings herein. Furthermore, no limitations are intended to thedetails of construction or design herein shown, other than as describedin the claims below. It is therefore evident that the particularembodiments disclosed above may be altered or modified and all suchvariations are considered within the scope and spirit of the invention.Accordingly, the protection sought herein is as set forth in the claimsbelow.

The invention claimed is:
 1. An apparatus for treating a patient toimprove cardiac performance and efficiency of the patient's heart, theapparatus comprising: at least one electrode adapted to be located in aregion associated with nervous tissue in a patient; means for monitoringone or more physiologic parameters of the patient; means forautomatically applying electrical stimulation via the at least oneelectrode to improve balance of a neuro-endocrinological system of thepatient in response to the one or more physiologic parameters of thepatient; and means for delivering a pacing therapy to the patient'sheart of a type that improves cardiac output, wherein said pacingtherapy consists of a cardiac resynchronization therapy; and means foradjusting the electrical stimulation applied during delivery of thepacing therapy responsive to the one or more physiological parameters ofthe patient as monitored during delivery of the pacing therapy.
 2. Theapparatus of claim 1, wherein the at least one electrode furthercomprises at least one implanted electrode adapted to be locatedadjacent a patient's spine.
 3. The apparatus of claim 1, wherein the atleast one electrode is adapted to be located external to and in directcontact with a portion of skin of the patient's.
 4. The apparatus ofclaim 1, wherein the at least one electrode is adapted to be located ina subcutaneous space of the patient's body.
 5. The apparatus of claim 1wherein delivery of the pacing therapy comprises altering a previouslydelivered pacing therapy in conjunction with applying the electricalstimulation.
 6. The apparatus of claim 1 wherein delivery of the pacingtherapy comprises initiating delivery of the pacing therapy inconjunction with applying the electrical stimulation.
 7. The apparatusof claim 1 wherein the monitoring means comprises a pressure sensor. 8.The apparatus of claim 1 wherein the monitoring means comprises apressure sensor adapted for a cardiac location.
 9. The apparatus ofclaim 8 wherein the monitoring means comprises means for determining thepatient's diastolic pressure.
 10. The apparatus of claim 1 wherein themonitoring means comprises means for sensing heart rate.
 11. Theapparatus of claim 10 wherein the monitoring means comprises means forsensing heart rate variability.